Risk Factors for Nonplatelet Thromboxane Generation After Coronary Artery Bypass Graft Surgery

BACKGROUND: Persistent thromboxane (TX) generation while receiving aspirin therapy is associated with an increased risk of cardiovascular events. The Reduction in Graft Occlusion Rates (RIGOR) study found that aspirin-insensitive TXA2 generation, indicated by elevated urine 11-dehydro-TXB2 (UTXB2) 6 months after coronary artery bypass graft surgery, was a potent risk factor for vein graft thrombosis and originated predominantly from nonplatelet sources. Our goal was to identify risks factors for nonplatelet TXA2 generation. METHODS AND RESULTS: Multivariable modeling was performed by using clinical and laboratory variables obtained from 260 RIGOR subjects with verified aspirin-mediated inhibition of platelet TXA2 generation. The strongest variable associated with UTXB2 6 months after surgery, accounting for 47.2% of the modeled effect, was urine 8-iso-prostaglandin (PG)F2alpha, an arachidonic acid metabolite generated nonenzymatically by oxidative stress (standardized coefficient 0.442, P \u3c 0.001). Age, sex, race, lipid therapy, creatinine, left ventricular ejection fraction, and aspirin dose were also significantly associated with UTXB2 (P \u3c 0.03), although they accounted for only 4.8% to 10.2% of the modeled effect. Urine 8-iso-PGF2alpha correlated with risk of vein graft occlusion (odds ratio 1.67, P=0.001) but was not independent of UTXB2. In vitro studies revealed that endothelial cells generate TXA2 in response to oxidative stress and direct exposure to 8-iso-PGF2alpha. CONCLUSIONS: Oxidative stress-induced formation of 8-iso-PGF2alpha is strongly associated with nonplatelet thromboxane formation and early vein graft thrombosis after coronary artery bypass graft surgery. The endothelium is potentially an important source of oxidative stress-induced thromboxane generation. These findings suggest therapies that reduce oxidative stress could be useful in reducing cardiovascular risks associated with aspirin-insensitive thromboxane generation

Brachial Flow-Mediated Dilation and Incident Atrial Fibrillation The Multi-Ethnic Study of Atherosclerosis

Objective—It is unknown whether endothelial dysfunction precedes atrial fibrillation (AF) development. The objective of this study was to examine the association of brachial flow-mediated dilation (FMD) with incident AF. Approach and Results—A total of 2936 participants (mean age, 61±9.9 years; 50% women; 66% nonwhites) from the Multi-Ethnic Study of Atherosclerosis with available ultrasound brachial FMD measurements who were free of baseline AF were included in this analysis. Baseline (2000–2002) FMD was computed from the percentage difference (%FMD) in brachial artery diameter and maximum diameter during measured vasodilator response. AF was ascertained from hospitalization data including Medicare claims during a median follow-up of 8.5 years. Probability-weighted Cox proportional-hazards regression was used to compute hazard ratios and 95% confidence intervals for the association between FMD as a continuous variable (%FMD values per 1-SD increase) and incident AF. Incident AF was detected in 137 (4.7%) participants. Those with %FMD values below the sex-specific median value (median %FMD; men, 3.6%; women, 4.2%; incidence rate per 1000 person-years, 7.3; 95% confidence interval, 5.9–9.0) were more likely to develop AF than people whose %FMD values were above the median value (incidence rate per 1000 person-years, 4.5; 95% confidence interval, 3.4–5.8; log-rank P=0.0043). In a multivariable Cox regression analysis, each 1-SD increase in %FMD values (SD, 2.8%) was associated with less incident AF (hazard ratio, 0.84; 95% confidence interval, 0.70–0.99). These results were consistent across subgroups stratified by age, sex, and race/ethnicity. Conclusions—Smaller brachial FMD values are associated with higher rates of AF, sugge

Peripheral Arterial Disease and Risk of Atrial Fibrillation and Stroke: The Multi�Ethnic Study of Atherosclerosis

Background Peripheral arterial disease (PAD) shares several risk factors with atrial fibrillation (AF), and persons with PAD have an increased risk of stroke. It is unclear if PAD is associated with an increased risk for AF and whether this potential association explains the increased risk of stroke observed in those with PAD. Methods and Results We examined the association between PAD, measured by ankle�brachial index (ABI), and incident AF and incident stroke, separately, in 6568 participants (mean age 62±10 years, 53% women, 62% nonwhite) from the Multi�Ethnic Study of Atherosclerosis (MESA). ABI values 1.4 defined PAD. AF was ascertained through review of hospital discharge records and from Medicare claims data until December 31, 2010. An independent adjudication committee ascertained stroke events. Cox regression was used to estimate hazard ratios and 95% CIs for the association between PAD and AF and stroke. Over a median follow�up of 8.5 years, 301 (4.6%) participants developed AF and 140 (2.1%) developed stroke. In a model adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, PAD was associated with an increased risk of AF (hazard ratio 1.5, 95% CI 1.1 to 2.0). In a similar model, PAD was associated with incident stroke (hazard ratio 1.7, 95% CI 1.1 to 2.5), and the magnitude of risk was not different after inclusion of AF as a time�dependent covariate (hazard ratio 1.7, 95% CI 1.1 to 2.5). Conclusions PAD is associated with an increased risk of AF and stroke in MESA. Potentially, the relationship between PAD and stroke is not mediated by AF

Relations Between Depressive Symptoms, Anxiety, and T Wave Abnormalities in Subjects Without Clinically-Apparent Cardiovascular Disease (from the Multi-Ethnic Study of Atherosclerosis [MESA])

The aim of this study was to test the hypothesis that depression and anxiety are associated with electrocardiographic (ECG) repolarization abnormalities in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort free of symptomatic cardiovascular disease. Depressive symptoms were assessed by using the Center for Epidemiologic Studies Depression Scale and trait anxiety symptoms by using the Spielberger State-Trait Anxiety Inventory; both were categorized according to uppermost quartile. T-wave inversions in ECG leads other than V1 to V3 were obtained from electrocardiograms obtained at rest during the baseline examination. Participants with major intraventricular conduction abnormalities and those taking antiarrhythmics, antidepressants, and/or antipsychotics were excluded. Logistic regression models were estimated with multivariable adjustment for traditional cardiovascular disease risk factors. Among 5,906 participants, elevated depressive symptoms were associated with increased odds of T-wave inversion after multivariable adjustment (odds ratio 2.02, 95% confidence interval 1.33 to 3.06, p = 0.001), whereas greater trait anxiety was associated with reduced odds of T-wave inversion (odds ratio 0.47, 95% confidence interval 0.29 to 0.77, p = 0.003). The divergent associations of depressive symptoms and trait anxiety with ECG T-wave inversions were similar in men and women, and these associations were present across the racial and ethnic subgroups (non-Hispanic white, African-American, Hispanic, and Chinese). In conclusion, symptoms of depression and anxiety were independently yet oppositely associated with ECG T-wave inversions. Negative emotions may have a differential impact on cardiovascular mortality through unique relations with cardiac repolarization

Clinical care recommendations for cardiologists treating adults with myotonic dystrophy

Myotonic dystrophy is an inherited systemic disorder affecting skeletal muscle and the heart. Genetic testing for myotonic dystrophy is diagnostic and identifies those at risk for cardiac complications. The 2 major genetic forms of myotonic dystrophy, type 1 and type 2, differ in genetic etiology yet share clinical features. The cardiac management of myotonic dystrophy should include surveillance for arrhythmias and left ventricular dysfunction, both of which occur in progressive manner and contribute to morbidity and mortality. To promote the development of care guidelines for myotonic dystrophy, the Myotonic Foundation solicited the input of care experts and organized the drafting of these recommendations. As a rare disorder, large scale clinical trial data to guide the management of myotonic dystrophy are largely lacking. The following recommendations represent expert consensus opinion from those with experience in the management of myotonic dystrophy, in part supported by literature-based evidence where available

Clinical care recommendations for cardiologists treating adults with myotonic dystrophy

Myotonic dystrophy is an inherited systemic disorder affecting skeletal muscle and the heart. Genetic testing for myotonic dystrophy is diagnostic and identifies those at risk for cardiac complications. The 2 major genetic forms of myotonic dystrophy, type 1 and type 2, differ in genetic etiology yet share clinical features. The cardiac management of myotonic dystrophy should include surveillance for arrhythmias and left ventricular dysfunction, both of which occur in progressive manner and contribute to morbidity and mortality. To promote the development of care guidelines for myotonic dystrophy, the Myotonic Foundation solicited the input of care experts and organized the drafting of these recommendations. As a rare disorder, large scale clinical trial data to guide the management of myotonic dystrophy are largely lacking. The following recommendations represent expert consensus opinion from those with experience in the management of myotonic dystrophy, in part supported by literature-based evidence where available